Aims/hypothesis Sirtuin 1 (SIRT1) is a longevity-associated protein, which regulates energy metabolism and lifespan in response to nutrient deprivation. It has been proposed to be a therapeutic target for obesity and metabolic syndrome. We investigated whether α-lipoic acid (ALA) exerts a lipidlowering effect through regulation of SIRT1 activation and production in C 2 C 12 myotubes. Methods ALA-stimulated AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC), adipose triacylglycerol lipase (ATGL) and fatty acid synthase (FAS) production, as well as intracellular triacylglycerol accumulation and fatty acid β-oxidation were analysed in the absence or presence of a SIRT1 inhibitor (nicotinamide), SIRT1 small interfering (si) RNA and an AMPK inhibitor (compound C) in C 2 C 12 myotubes. Mice with streptozotocin/nicotinamideinduced diabetes and db/db mice fed on a high-fat diet were used to study the ALA-mediated lipid-lowering effects in vivo.Results ALA increased the NAD + /NADH ratio to enhance SIRT1 activity and production in C 2 C 12 myotubes. ALA subsequently increased AMPK and ACC phosphorylation, leading to increased palmitate β-oxidation and decreased intracellular triacylglycerol accumulation in C 2 C 12 myotubes. In cells treated with nicotinamide or transfected with SIRT1 siRNA, ALA-mediated AMPK/ACC phosphorylation, intracellular triacylglycerol accumulation and palmitate β-oxidation were reduced, suggesting that SIRT1 is an upstream regulator of AMPK. ALA increased ATGL and suppressed FAS protein production in C 2 C 12 myotubes. Oral administration of ALA in diabetic mice fed on a high-fat diet and db/db mice dramatically reduced the body weight and visceral fat content. Conclusions/interpretation ALA activates both SIRT1 and AMPK, which leads to lipid-lowering effects in vitro and in vivo. These findings suggest that ALA may have beneficial effects in the treatment of dyslipidaemia and obesity.
Undaria pinnatifada has been used as a natural diet food with few calories and as a source of iodine. Even though U. pinnatifida has been regarded as a diet food, the mechanisms of its inhibitory effects on adipocyte differentiation and the accumulation of fat in adipocytes are poorly understood. In this study, the effect and mechanism of U. pinnatifida ethanol extract on 3T3-L1 differentiation into adipocytes were investigated. The effects of U. pinnatifida ethanol extract on cell viability and the anti-adipogenic effect were investigated via MTT assay, Oil red O staining, RT-PCR, and western blot. The U. pinnatifida ethanol extract did not show toxicity up to a concentration of 50 μg/ml. The addition of U. pinnatifida ethanol extract decreased triglyceride contents by 40% when 50 μg/ml of U. pinnatifida ethanol extract was added during 3T3-L1 differentiation and adipocyte triglyceride formation. The transcription and expression of peroxisome proliferator-activated receptor γ (PPARγ), leptin, and hormone-sensitive lipase (HSL) as adipocyte-specific proteins were determined by RT-PCR and western blot. The overexpression of PPARγ could accelerate adipocyte differentiation. Also, leptin was secreted for triglyceride accumulation in the adipocytes and the increase of adipocyte cell size. Thus, PPARγ and leptin were used as indicators of obesity. PPARγ and leptin were repressed by the increased addition of U. pinnatifida ethanol extract. This indicates that U. pinnatifida was effective as an anti-obesity agent by repressing the differentiation of 3T3-L1 into adipocytes and inhibiting triglyceride formation in adipocytes.
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